There is strong evidence that the world-wide distribution of colon cancer and other diseases of the gastrointestinal tract are highly correlated with dietary habits. Moreover, it has been hypothesized that intestinal anaerobic bacteria are enzymatically generating carcinogens or co-carcinogens from bile acids. The long term objective of the proposed research is to determine the factor(s) that regulate the enzymatic conversion of bile acids by intestinal anaerobic bacteria and the physiological significance of these reactions and products to the bacteria and host. The first two goals will be to purify and characterize thoroughly the various bile salt catabolic enzymes and uptake or binding systems in selected DNA homology groups of Bacteroides fragilis by using established biochemical methods. Moreover, the regulation of biosynthesis of these enzymes and uptake systems will be characterized. The third goal will be to determine the distribution of these ezymes and uptake systems in different DNA homology groups of B. fragilis. The fourth goal will be to determine the rates of bile acid and bile salt conversion in cell cultures of B. fragilis throughout the different stages of growth under conditions of controlled pH and carbohydrate concentration. The bile acid conversion products will be quantitated by using a radioassay as well as by using purified 7-alpha- hydroxysteroid dehydrogenase and 3-alpha-hydroxysteroid dehydrogenase.